Extrusion/spheronization is a relatively complex technique used for the preparation of pharmaceuticals in the form of beads or spheroids (0.5-1.5 mm in diameter). The process of manufacture involves dry blending drug and excipients, wet granulation (aqueous or non-aqueous) of the mass, extrusion through a screen of defined pore size and spheronization. During the extrusion process, the wet mass is formed and compacted into cylindrical strands. To obtain spheres, the cylindrical strands are placed in a spheronizer, which is simply a unit containing a rotating disc. The cylindrical strands break up under the action of the rotating disc, and the short strands deform to form spheres, by a tumbling/roping action.
To undergo this process, it is recognized that the blend of drug and excipients should exhibit a high degree of plasticity to allow the extrusion and spheronization (deformation) process to occur. To achieve the required plasticity Avicel (microcrystalline cellulose, of various grades, PH 101, PH 102, PH 103, PH 105, RC 591, RC 581 CL-611) is added to the blend. In addition, the fluid used in wet massing adds plasticity to the blend; the wetter the mass the more plastic the blend becomes. However, fluid levels need to be carefully controlled, as agglomeration (balling up) will occur during spheronization of an over wet extrudate.
It has been found that for a blend of drug and excipients to achieve an acceptable degree of plasticity to allow the extrusion and spheronization process to occur, the blend should not contain more than 75-80% by weight of the drug component and should not contain less than 15-20% of a microcrystalline cellulose component. Gamlen, M. J., Manuf. Chem., June, 1985, p. 55 and O'Connor, R. E. and Schwartz, J. B., Drug Dev. Ind. Pharm. II, 1837, 1985.
Although the above-described prior art extrusion/spheronization technique is satisfactory to produce beads containing drug loads of up to 75 to 80%, still, there is a need for beads containing more than 80% drug. Thus, for example, it has been found that erythromycin beads containing 70 to 75% erythromycin and 15 to 20% microcrystalline cellulose may not have the desired drug dissolution rate due to the presence of the large amounts of microcrystalline cellulose; in addition, the drug dose would not fit comfortably into a size 0 capsule.